CA2956464C - Inhibiteurs a base de bisamidinium pour le traitement de la dystrophie myotonique - Google Patents
Inhibiteurs a base de bisamidinium pour le traitement de la dystrophie myotonique Download PDFInfo
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- CA2956464C CA2956464C CA2956464A CA2956464A CA2956464C CA 2956464 C CA2956464 C CA 2956464C CA 2956464 A CA2956464 A CA 2956464A CA 2956464 A CA2956464 A CA 2956464A CA 2956464 C CA2956464 C CA 2956464C
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- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 235000003499 redwood Nutrition 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 231100000338 sulforhodamine B assay Toxicity 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960004906 thiomersal Drugs 0.000 description 1
- 125000000464 thioxo group Chemical group S=* 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Chemical group 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention concerne des composés de formule (I), des compositions et des méthodes thérapeutiques. Les composés et les compositions peuvent être utilisés par le traitement de l'atrophie myotonique. Les composés peuvent sélectivement être liés aux répétitions de CUG dans l'ARN ou de CTG dans l'ADN et inhibe la réplication des acides nucléiques. Des agents thérapeutiques ciblant l'ARN pour le traitement de l'atrophie myotonique de type 1 (DM1) sont décrits. Selon un mode de réalisation, deux liants de bisamidinium sont liés au moyen de la chimie click pour former un hétérodimère qui est un inhibiteur puissant du complexe MBNLl-rCUGexp (Ki = 25 ± 8 nM) et relativement non toxique pour les cellules HeLa, dissout les foyers nucléaires, corrige >80 % de l'épissage alternatif à infrarouge mal régulé dans les cellules du modèle DML (1 µM) et montre une amélioration des phénotypes de maladies dans le modèle de la drosophile DML
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462034932P | 2014-08-08 | 2014-08-08 | |
| US62/034,932 | 2014-08-08 | ||
| PCT/US2015/044526 WO2016023039A1 (fr) | 2014-08-08 | 2015-08-10 | Inhibiteurs à base de bisamidinium pour le traitement de la dystrophie myotonique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2956464A1 CA2956464A1 (fr) | 2016-02-11 |
| CA2956464C true CA2956464C (fr) | 2023-05-09 |
Family
ID=55264707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2956464A Active CA2956464C (fr) | 2014-08-08 | 2015-08-10 | Inhibiteurs a base de bisamidinium pour le traitement de la dystrophie myotonique |
Country Status (3)
| Country | Link |
|---|---|
| US (2) | US10266520B2 (fr) |
| CA (1) | CA2956464C (fr) |
| WO (1) | WO2016023039A1 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3552571B8 (fr) | 2014-05-18 | 2024-10-30 | Eximo Medical Ltd. | Système d'ablation de tissus à l'aide d'un laser pulsé |
| US11242326B2 (en) | 2017-08-25 | 2022-02-08 | The Board Of Trustees Of The University Of Illinois | Multivalent ligand for myotonic dystrophy |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2698865B2 (ja) | 1994-08-08 | 1998-01-19 | 仲昭 大澤 | 筋緊張性ジストロフィー症治療剤 |
| US20050037954A1 (en) | 2001-03-23 | 2005-02-17 | Masaki Hirashima | Novel agents for ameliorating motor disorder |
| US6987123B2 (en) | 2001-07-26 | 2006-01-17 | Cadila Healthcare Limited | Heterocyclic compounds, their preparation, pharmaceutical compositions containing them and their use in medicine |
| GB0613518D0 (en) | 2006-07-06 | 2006-08-16 | Phytopharm Plc | Chemical compounds |
| EP2129388B1 (fr) * | 2007-02-23 | 2012-09-12 | The Research Foundation Of State University Of New York | Composés de ciblage d'arn, et procédés de fabrication et d'utilisation de ceux-ci |
| WO2009105691A2 (fr) * | 2008-02-21 | 2009-08-27 | State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Utilisations de pentamidine et de composés associés |
| US8754084B2 (en) * | 2012-03-27 | 2014-06-17 | The Board Of Trustees Of The University Of Illinois | Therapeutic methods and agents for treating myotonic dystrophy |
-
2015
- 2015-08-10 WO PCT/US2015/044526 patent/WO2016023039A1/fr not_active Ceased
- 2015-08-10 CA CA2956464A patent/CA2956464C/fr active Active
- 2015-08-10 US US15/502,474 patent/US10266520B2/en active Active
- 2015-08-10 US US14/822,796 patent/US9376421B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20180215736A1 (en) | 2018-08-02 |
| CA2956464A1 (fr) | 2016-02-11 |
| US20160052914A1 (en) | 2016-02-25 |
| WO2016023039A1 (fr) | 2016-02-11 |
| US10266520B2 (en) | 2019-04-23 |
| US9376421B2 (en) | 2016-06-28 |
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